Radiation risks at low doses remain a hotly debated topic. Recent experimental advances in our understanding of effects occurring in the progeny of irradiated cells, and/or the non-irradiated neighbors of irradiated cells (i.e., non-targeted effects associated with exposure to ionizing radiation), have influenced this debate. The goal of this document is to summarize the current status of this debate and speculate on the potential impact of non-targeted effects on radiation risk assessment and the radiation dose response profile.